Transforming growth factor beta 1 (TGF-b1) induces growth suppression in a variety of cell types. The signaling molecules that are responsible for transmitting TGF-b signal include Smad2, 3, and 4. Upon TGF-b engagement, Smad2 and 3 become phosphorylated and form heteromeric complexes with Smad4 and translocate to nucleus, where in association with transcriptional co-activators or repressors, binds to the promoters of TGF-b-responsive genes. In our laboratory, we are studying a diffuse large B-cell lymphoma cell line, DB that lacks TGF-b responsiveness with respect to growth suppression. Our goal is to identify the deficit(s) in TGF-b signaling pathway in DB cells. Preliminary data indicate that the TGF-b-mediated phosphorylation of Smad2 and Smad3 were absent in DB cells, whereas TGF-b-induced phosphorylation of both Smad3 and Smad2 were observed in a TGF-b-responsive B-cell lymphoma cell line RL. Examination of the status of the TGF-b receptors reveals that both RL and DB cells have TGF-b receptors I on their cell surface, whereas TGF-b receptors II were present only on the cell surface of RL cells, but not on DB cells. Although the TGF-b receptors II were absent on the cell surface, they were present in the cytoplasm. We are currently investigating the mechanism underlying the deficit in translocation of receptors II to the cell surface, and how this lack of translocation can be corrected to render the cells responsive to TGF-b treatment.